Over the past five years, we have established a framework for a training program focused on the field of regenerative medicine, as it relates to musculoskeletal disease. We created a program of interdisciplinary musculoskeletal regenerative medicine teams composed of i) a training faculty, ii)) a clinical/surgeon faculty mentor and iii) a trainee. Investigational focus has been on a diverse but interrelated group of projects that consider the reconstitution of injured or missing musculoskeletal tissues with cells, scaffolds and bioactive molecules through: 1) application of findings from developmental biology to treat pediatric disorders, ii) the development and use of bioinformatics technologies to uncover new therapeutic possibilities and iii) strategies to combat the rejection of allogeneic tissue transplants. In this renewal application, we propose to expand our program from its current scope of four postdoctoral trainee positions to five postdoctoral trainees, one of which is reserved for an orthopaedic surgery postdoctoral fellow. We will continue to focus training efforts on Ph.D.'s and M.D.'s intent on a career in interdisciplinary academic regenerative-restorative medicine. The first primary goal will be to provide trainees with combinatorial skill sets in: 1) stem cell and developmental biology; 2) molecular genetics; 3) tissue engineering and materials science; 4) state-of the-art technologies in high-throughput, large scale computational science; and 5) clinical-translational medicine that can be layered on top of their preceding undergraduate and graduate training in one of these areas. The second primary goal will be to educate trainees in an integrated approach to regenerative medicine with hands-on project-oriented teaching in how to i) build, ii) operate in and iii) modify a multidisciplinary tem of colleagues. Our current track record indicates that this team approach has enabled our trainees to receive a comprehensive bench-to-bedside experience in what is required to actualize a bioengineered therapeutic in real world terms. This translational research structure is currently supported by a robust collection of didactic curricula and seminar series designed to introduce and refine the skills needed by postdoctoral trainees to understand, design, compose, undertake and earn extramural financial support for a research project in regenerative medicine. In addition to dedication to providing training to surgeon scientists in basic research, in this renewal increased focus will be placed on exposure of Ph.D. trainees to highly relevant clinical challenges through attendance at grand rounds and attendance/observation of the clinical activities of the trainee's clinical faculty mentor. The T32 research and didactic training program is designed to provide individual trainees two years of funding in preparation for their transition into more specialized training and alternative sources of support.